Moderate to severe non-penetrating pediatric traumatic brain injury (TBI) compromises distributed neural networks by disrupting axonal connections contributing to cognitive impairments. Cognitive functioning improves significantly over the first year post-TBI relative to the post-acute period in the vast majority of pediatric TBI survivors. There is evidence of restitution of neural connectivity over the first year post-TBI. The central hypothesis of this proposal is that cognitive deficits after non-penetrating pediatric TBI reflect white matter injury and disconnection, and that cognitive recovery occurs in conjunction with the restoration of neural network connectivity. Connectivity will be assessed using both structural brain imaging (MRI and DTI) and functional (electrophysiological, fMRI and neuropsychological) methods. We will study the structure and function of brain systems that are particularly vulnerable to white matter (WM) disruptions caused by TBI. The corpus callosum (CC) and a frontal-temporal-parietal (FTP) network that subserves spatial working memory will be studied as exemplars of neural networks disrupted by TBI. Innovative methods from behavioral neuroscience and neuroimaging will be used to assess the function of these networks, including separate measures of anterior and posterior CC function. Structural measures, including MRI and DTI, will be used to assess regional WM changes. The functional and structural measures will be administered longitudinally in 60 children with moderate/severe TBI and 60 age and gender matched controls. Children will be studied post-acutely (2-4 months post-TB I) and chronically (12 months post injury) to test the hypothesis that neurocognitive recovery following TBI is associated with increased WM connectivity and volume. This project will develop methods for studying brain/behavior relations in the CC following TBI that can be translated into experimental studies of small animals to help develop novel therapies. By explicating mechanisms that underlie naturally-occurring white matter injury and repair, the proposed project will identify potential new targets for interventions designed to accelerate the process of neurocognitive recovery. PUBLIC HEALTH RELEVANCE: Children with moderate-severe traumatic brain injuries will be studied 2-4 months and at 12 months post-injury to test the hypothesis that neurocognitive recovery following TBI is associated with increased white matter connectivity and volume. Innovative brain imaging and behavioral neuroscience methods will be used to assess changes in brain structure and function following pediatric TBI. By explicating mechanisms that underlie naturally-occurring white matter injury and repair, the proposed project will identify potential new targets for interventions designed to accelerate the process of neurocognitive recovery.